Solid-phase organic synthesis involves deliberately performing chemical reactions in heterogeneous rather than homogeneous media. The origins of the technology are attributed to Robert Merrifield and Robert Letsinger. Merrifield developed methods of automating the synthesis of peptides on minute, insoluble, chemically-inert polymer beads, for which he won the Nobel Prize in 1984. In parallel findings, Robert Letsinger of Northwestern University developed polynucleotide synthesis on solid phases, which led to the development of the DNA synthesis machines.
The solid phase method has inherent advantages in some synthetic processes, in that undesirable by-products may be removed easily by filtration and yields of reaction may be higher. Other advantages include the immobilization of odiferous and/or environmentally dangerous materials, and the recovery of optically-active materials. Using this basic platform, drug companies are using solid phase organic synthesis in a process called combinatorial chemistry. This process is used to prepare thousands of possible drugs simultaneously for rapid biological screening
In spite of the power of modern solid-phase synthesis techniques, there is still much room for improvement. In particular, even the best solid-phase synthesis methods result in some failure sequences, which ultimately limit the ability to synthesize long polymer chains of high purity. It would be desirable to have available a technique which addresses these limitations, allowing for the synthesis of longer chains of higher purity.
It would also be desirable to have solid-phase synthesis techniques that facilitate the preparation of capillaries having polymers attached to the internal surface of the capillary. For example, such capillaries would be useful in a variety of extraction processes that employ extraction capillaries having extraction groups attached to the capillary. In certain applications, it would be advantageous to synthesize the extraction polymer directly on the internal surface of the capillary, i.e., in situ synthesis, rather than the standard technique of synthesizing the polymer and then attaching the fully formed polymer to the capillary.
Accordingly, the need exists for improved methods and reagents for solid phase synthesis and/or methods of performing solid phase synthesis directly on the internal surface of a capillary. The present invention addresses this need by providing new methods and reagents for performing solid-phase synthesis on the internal surface of a capillary column.